Our long-term goal is to define mechanisms by which intestinal epithelial wounds reseal. Damage to the epithelium in pathologic states such as inflammatory bowel disease, ischemia and infection result in tissue exposure to luminal pathogens/antigens and in fluid/electrolyte loss. Epithelial cells can rapidly migrate to cover denuded surfaces by a process called "restitution." Our hypothesis is that dynamic restructuring of the actin cytoskeleton, focal cell-matrix & cell-cell associations are central events in restitution and are regulated by the family of RhoGTPases. First, will analyze role of Rho GTPases in mediating polarized restructuring of the actin cytoskeleton and focal cell-matrix associations. Secondly, we will examine the role of Junctional Adhesion Molecule in restitution. Our approach will include a broad spectrum of cell biological techniques such as confocal microscopy, biochemistry and transfection. Such studies will provide important insights into the molecular mechanisms of restitution which will provide a basis for therapeutics aimed at promoting wound closure.